User:NKuldell/Q/A working page

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Disclaimer: This page is a work in progress but it may be a good place for Reshma, Barry and I to collaborate. No one should consider these complete or authoritative.

Question: How is synthetic biology different from existing, related fields like genetic engineering and metabolic engineering?

Answer: In some ways, nothing. People have been rationally modifying genetic material for much of recorded history. The new part is that now we have full sequence information for many of the planet's organisms AND we have ways to make the genetic material from scratch. Everyday, there are more bugs, plants and animals whose DNA is being sequenced. And everyday, the chance to synthesize that DNA from scratch moves closer to becoming a cheap and reliable option. Synthetic biology makes use of these developments, assembling available sequence information from the living world in rational and useful ways.(NK)

Synthetic Biology also places a greater emphasis on the *engineering* than fields like genetic engineering and metabolic engineering. Fundamentally, engineering disciplines try to make use of standard components that can be assembled in different ways to construct novel systems. Thus currently, synthetic biology seeks to build the foundations for engineering biology. The power of such an approach is that it allows people to build upon each other's work to an extent not possible in other disciplines which are more focused on one-off designs (like genetic engineering and metabolic engineering). Synthetic biology which emphasizes the design and manufacturing aspects of the field should make future efforts to engineer biology easier. (RS)

Some current examples of synthetic biology, however, place less emphasis on foundations and standards of engineering, and in these cases synthetic biology may be better regarded as a specialty of biological engineering, with metabolic and genetic engineering as other complimentary specialities. By analogy, mechanical engineering could be an umbrella descriptor with automotive engineering, internal combustion engine design and headlamp design included as specializations within mechanical engineering. (from BC, though I'm afraid I haven't really captured your idea well. Please correct!! Thanks-NK).

Question: While their methods are different, the end results of synthetic biology and genetic engineering seem similar: new organisms that are not seen in nature. If that is true, does it follow that synthetic biology is not bringing substantially new risks onto the scene?

The risks and rewards are likely different. If synthetic biology is wildly successful then a 4-year old child could build something cool with biological materials, whereas genetic engineering as it’s currently performed requires good technical understanding of the project, and access to specialized resources such as a lab bench and reagents. In the future, novel biological systems may be built with limited know-how, limited budget and no specialized facility.

Question: With Synthetic Biology can anyone be a biological engineer?

Answer: Synthetic Biology is still new and has a long way to go before garage biohackers can make something as useful and profitable as what you've suggested. Most of the people doing the work are housed in academic and industrial institutions around the world. Putting bits of DNA code together in useful ways is tricky to do and needs some special equipment that's probably not in your kitchen or basement. Biohacking today is also pretty expensive and often unsuccessful. In a few years it may be easy and cheap enough for anyone to piece together any living creature of their imagination.

Question: Why is biology so hard to engineer now?

This futuristic state will be reached only by rectifying two imbalances. Currently there is a wealth of sequence information available but limited ways to make experimental use of it. Additionally, we have a good understanding of basic cellular activities but only a few approaches to predictably combine activities in creative and re-useable ways. Both imbalances may be rectified through synthetic biology, for example with inexpensive and fast methods for DNA synthesis and with improved foundational technologies for reusing genetic elements. Thus SB brings with it new risks and rewards. It will be easy and cheap to make something not seen in nature, which means it will be done by folks who haven’t had the technology of genetic engineering at their disposal.

Question: Some people may foresee a day when Synthetic Biology can build complex organisms from basic biological materials. Can simple viruses and primitive life forms already now be synthesized?

Answer: Viruses have been synthesized. Life forms, not yet. For example, in 2002 Cello, Paul and Wimmer reported the successful de novo synthesis of poliovirus (Science 297:1016), creating from raw chemicals an agent that could infect mice, albeit with a whopping dose relative to the natural virus that leads to infection. The authors described their efforts as “fueled by a strong curiosity about the minute particles that we can view both as chemicals and as “living” entities.” Other examples of de novo synthesis of viruses are the phiX174 bacteriophage reported in 2003 (PNAS 100:15440) and human influenza (Science 310:77) in 2005. Noteworthy are the speed with which these viruses could be made, a mere two weeks from raw chemicals to infectious bacteriophage in 2003, as well as the technology’s potential for dual-use (e.g. Nature 2006 439:266).

Since viruses replicate only in living hosts, they are not themselves alive. A minimal life form would require self-replicating nucleic acids and a synthetic chassis in which to house them. A front-runner for the former is RNA with catalytic activity, including self-replication as described in 2001 (Science 292:1319). For the latter, lab built- membrane vesicles to encapsulate RNA were described in 2005(J Am Chem Soc 127:13213), but these assemble only through directed manipulations of experimental conditions. Thus, it seems efforts to enclose self-replicating nucleic acids in some spontaneously assembling bubble are underway but, to date, only components of a lab-generated living cell have been reported (http://www.pbs.org/wgbh/nova/sciencenow/3214/01.html)

Question: What kinds of systems can be built via Synthetic Biology that can't be built using other technologies?

Answer (to somewhat different question): There are some folks who want to re-write the genetic code from living creatures just like computer programmers might want to re-write the code for your PC, annotating their changes and making each element of code more manipulable. Examples of this include T7.1, two genomes in one cell and Blattner minimal coli. Other synthetic biologists are engineering the metabolism of simple organisms like bacteria or yeast to make therapeutic compounds whose natural reservoirs are in short supply. Recent success in this effort is artemisinen. Finally, synthetic biology can also be a great option for regular, old fashioned biologists who might like to test their existing models by building them from the ground up. This is akin to efforts in chemical engineering that

Question: What are the perceived benefits of Synthetic Biology? Who is investing in this and what do they see as the pay-off? Why would someone invest in this area as opposed to more traditional Genetic Engineering efforts?